Drug-Induced Acute Liver Injury Due to Tamoxifen Prophylaxis

Abstract

A 41-year-old female was diagnosed with stage II ductal breast cancer in November 2023. The patient subsequently underwent a bilateral mastectomy and was started on tamoxifen 20 mg as post-operative adjuvant therapy in December 2023. Surveillance positron emission tomography (six months post-mastectomy) confirmed no cancer recurrence prior to symptom onset. Following abdominal pain, nausea and vomiting, pruritus, and jaundice, in the context of an elevated bilirubin level and a 1.5 mm gallstone, tamoxifen treatment was discontinued in July 2024. In August 2024, the patient presented with recurrent nausea and vomiting, increased abdominal pain, worsening pruritus and jaundice, debilitating back pain, and a weight loss of 20.87 kg. The patient was admitted to the hospital for further workup. Her bilirubin levels were found to be 17.9 mg/dl (normal range: 0.1-1.2 mg/dL). Following subsequent labs and scans such as a hepatobiliary iminodiacetic acid scan, liver biopsy, computerized tomography of the lumbar spine, magnetic resonance imaging of the lumbar spine and bilateral hips, anti-smooth muscle antibody test, and more diagnostic testing, it was determined that the patient was suffering from drug-induced liver injury. After the initiation of steroids and ursodiol, her bilirubin measurements decreased. The patient reported resolution of symptoms a month later, as her bilirubin levels had declined from 17.9 to 2.3 mg/dL over four weeks. This unique presentation of tamoxifen-induced acute liver injury is reversible, and patients on tamoxifen need a frequent comprehensive metabolic panel to detect possible liver injury preemptively.

Keywords: bilirubin; cholestatic jaundice; drug-induced liver injury (dili); her-2 positive breast cancer; tamoxifen therapy.

Figure 1. Hepatobiliary iminodiacetic acid scan

The above images depict an abnormal scan. Gallbladder activity was not visualized during 60 minutes of sequential imaging. It was eventually visualized at 270 minutes (white arrows) and hence deemed to be consistent with chronic cholecystitis. Anterior view (A) and lateral view (B) are shown above. Additionally, delayed small bowel demonstration may represent partial common bile duct obstruction. Lastly, delayed washout of the radiotracer by the hepatic parenchyma was consistent with hepatocellular dysfunction.

Figure 2. Liver biopsy result of the patient

The above figure depicts a liver biopsy of this patient's tamoxifen-induced acute cholestatic liver injury. Cholestatic liver injury, generally clinically characterized by jaundice and pruritus, is accompanied by increases in serum alkaline phosphatase and serum bilirubin [4]. Liver biopsy is generally used to reliably evaluate damage to bile ducts and confirm cholestatic liver injury [4]. This is exemplified by the apparent inflammation with the presence of inflammatory cells, and lobular disarray as shown throughout in this figure.